Measuring healthy ageing: current and future tools.

Human ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration. As the population of the world grows older, placing significant strain on social and healthcare resources, there is a growing need to identify reliable and easy-to-employ markers of healthy ageing for early detection of ageing trajectories and disease risk. Such markers would allow for the targeted implementation of strategies or treatments that can lessen suffering, disability, and dependence in old age. In this review, we summarise the healthy ageing scores reported in the literature, with a focus on the past 5 years, and compare and contrast the variables employed. The use of approaches to determine biological age, molecular biomarkers, ageing trajectories, and multi-omics ageing scores are reviewed. We conclude that the ideal healthy ageing score is multisystemic and able to encompass all of the potential alterations associated with ageing. It should also be longitudinal and able to accurately predict ageing complications at an early stage in order to maximize the chances of successful early intervention.

Development of a layered bacterial nanocellulose-PHBV composite for food packaging.

BACKGROUND: Most of the current materials used in food packaging are synthetic and non-degradable, raising environmental issues derived from the accumulation of plastics in landfills/waterways. The food industry increasingly needs eco-friendly sustainable materials that meet food-packaging requirements. Bacterial nanocellulose (BNC), a biopolymer obtained by fermentation, offers very good mechanical properties and the ability to carry and deliver active substances. However, its water-vapor permeability is too high for food-packaging applications. In this work, a layered biodegradable composite based on BNC and polyhydroxyalkanoate (PHBV) was produced, attempting to improve its overall barrier properties. Polyhydroxyalkanoate is a biopolymer with high degree of hydrophobicity and biodegradability, and is also obtained by fermentation. Wet BNC membranes produced by static culture were plasticized by impregnation of solutions of either glycerol (BNCgly ) or polyethylene glycol (MW 600) (BNCPEG ). The plasticized BNC was then coated with PHBV solution dissolved in formic acid, and oven dried at 148 °C. RESULTS: Overall, PHBV coating on plasticized BNC reduced water vapor permeability significantly (from 0.990 to 0.032 g.µm.m-2 .day-1 .Pa-1 ) under 50% relative humidity. It increased the hydrophobicity (contact angle from 10-40° to 80-90°) but decreased the stiffness (from 3.1 GPa to 1.3 Gpa) of the composite. CONCLUSIONS: Overall, the mechanical and barrier properties of the layered composite obtained were considered suitable for food-packaging applications. The plasticizing (with glycerol or polyethylene glycol) of BNC significantly improved the mechanical performance and the PHBV coating reduced the water affinity (vapor and liquid state) on BNC. © 2022 Society of Chemical Industry.

Post-transcriptional silencing of Bos taurus prion family genes and its impact on granulosa cell steroidogenesis.

Prion proteins constitute a major public health concern, which has partly overshadowed their physiological roles in several scenarios. Indeed, these proteins were implicated in male fertility but their role in female fertility is relatively less explored. This study was designed to evaluate the role of SPRN and PRNP prion family genes in bovine follicular steroidogenesis pathways. Post-transcriptional SPRN and PRNP silencing with siRNAs was established in bovine granulosa cell (GC) in vitro culture, and gene expression and progesterone and estradiol concentrations were evaluated. SPRN knockdown, led to a downregulation of CYP11A1 mRNA levels (2.1-fold), and PRNP knockdown led to an upregulation of SPRN mRNA levels (2.3-fold). CYP19A1 expression and estradiol synthesis was not detected in any experimental group. Finally, SPRN knockdown led to a mild reduction in progesterone production in GCs and this was the only experimental group that did not exhibit an increment in progesterone levels after 48 h of culture. As a conclusion, it was possible to detect the expression of the SPRN gene in bovine GCs, a potential interaction between SPRN and PRNP regulation, and the impact of SPRN expression on CYP11A1 and progesterone levels. These findings bring new insights into the role of these genes in ovarian steroidogenesis and female reproductive physiology.

SARS-CoV-2 air sampling: A systematic review on the methodologies for detection and infectivity.

This systematic review aims to present an overview of the current aerosol sampling methods (and equipment) being used to investigate the presence of SARS-CoV-2 in the air, along with the main parameters reported in the studies that are essential to analyze the advantages and disadvantages of each method and perspectives for future research regarding this mode of transmission. A systematic literature review was performed on PubMed/MEDLINE, Web of Science, and Scopus to assess the current air sampling methodologies being applied to SARS-CoV-2. Most of the studies took place in indoor environments and healthcare settings and included air and environmental sampling. The collection mechanisms used were impinger, cyclone, impactor, filters, water-based condensation, and passive sampling. Most of the reviewed studies used RT-PCR to test the presence of SARS-CoV-2 RNA in the collected samples. SARS-CoV-2 RNA was detected with all collection mechanisms. From the studies detecting the presence of SARS-CoV-2 RNA, fourteen assessed infectivity. Five studies detected viable viruses using impactor, water-based condensation, and cyclone collection mechanisms. There is a need for a standardized protocol for sampling SARS-CoV-2 in air, which should also account for other influencing parameters, including air exchange ratio in the room sampled, relative humidity, temperature, and lighting conditions.

Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-ß (Aß) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.

CRISPR-based strategies in infectious disease diagnosis and therapy.

PURPOSE: CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases. METHODS: We searched Pubmed and Google Scholar for CRISPR-based strategies in the diagnosis and treatment of infectious diseases. Reference lists were reviewed and synthesized for narrative review. RESULTS: CRISPR-based strategies represent a novel approach to many challenging infectious diseases. CRISPR technologies can be harnessed to create rapid, low-cost diagnostic systems, as well as to identify drug-resistance genes. Therapeutic strategies, such as CRISPR systems that cleave integrated viral genomes or that target resistant bacteria, are in development. CRISPR-based therapies for emerging viruses, such as SARS-CoV-2, have also been proposed. Finally, CRISPR systems can be used to reprogram human B cells to produce neutralizing antibodies. The risks of CRISPR-based therapies include off-target and on-target modifications. Strategies to control these risks are being developed and a phase 1 clinical trials of CRISPR-based therapies for cancer and monogenic diseases are already underway. CONCLUSIONS: CRISPR systems have broad applicability in the field of infectious diseases and may offer solutions to many of the most challenging human infections.

Current and potential biomarkers in gastric cancer: a critical review of the literature.

Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. The following search terms were applied to PubMed as of December 2020: 'gastric cancer classification', 'gastric cancer epidemiology', 'cancer metastasis' and 'gastric cancer biomarker'. Only experimental studies were reported in the 'biomarkers' section. Some biomarkers can serve as therapeutic targets for antitumoral drugs. The genes analyzed include E-cadherin, RPRM, XAF1, MINT25, TFF1, p16 and p53. The miRNAs analyzed include miR-18a, miR185-5p, miR-125b and miR-21. Some molecules were associated with metastasis of gastric cancer, specifically those involved with EMT process and tissue degradation.

Lay abstract Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers are molecules that have different expressions in tumor cells than in normal body cells, and can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. Biomarkers in gastric cancer can include genes that suppress tumor progression, genes that increase tumor progression by binding to growth molecules, molecules related to the body's immune response to the tumor, and non-coding RNA molecules (RNA molecules that do not produce proteins but regulate the cell's genetic material). Some biomarkers can serve as therapeutic targets for anti-tumoral drugs.

Apparent temperature and heat-related illnesses during international athletic championships: A prospective cohort study.

International outdoor athletics championships are typically hosted during the summer season, frequently in hot and humid climatic conditions. Therefore, we analyzed the association between apparent temperature and heat-related illnesses occurrence during international outdoor athletics championships and compared its incidence rates between athletics disciplines. Heat-related illnesses were selected from illness data prospectively collected at seven international outdoor athletics championships between 2009 and 2018 using a standardized methodology. The Universal Thermal Climate Index (UTCI) was calculated as a measure of the apparent temperature based on weather data for each day of the championships. Heat-related illness numbers and (daily) incidence rates were calculated and analyzed in relation to the daily maximum UTCI temperature and between disciplines. During 50 championships days with UTCI temperatures between 15℃ and 37℃, 132 heat-related illnesses were recorded. Average incidence rate of heat-related illnesses was 11.7 (95%CI 9.7 to 13.7) per 1000 registered athletes. The expected daily incidence rate of heat-related illnesses increased significantly with UTCI temperature (0.12 more illnesses per 1000 registered athletes/°C; 95%CI 0.08-0.16) and was found to double from 25 to 35°C UTCI. Race walkers (RR = 45.5, 95%CI 21.6-96.0) and marathon runners (RR = 47.7, 95%CI 23.0-98.8) had higher heat-related illness rates than athletes competing in short-duration disciplines. Higher UTCI temperatures were associated with more heat-related illnesses, with marathon and race walking athletes having higher risk than athletes competing in short-duration disciplines. Heat-related illness prevention strategies should predominantly focus on marathon and race walking events of outdoor athletics championships when high temperatures are forecast.

Randomized Oblivious Transfer for Secure Multiparty Computation in the Quantum Setting.

Secure computation is a powerful cryptographic tool that encompasses the evaluation of any multivariate function with arbitrary inputs from mutually distrusting parties. The oblivious transfer primitive serves is a basic building block for the general task of secure multi-party computation. Therefore, analyzing the security in the universal composability framework becomes mandatory when dealing with multi-party computation protocols composed of oblivious transfer subroutines. Furthermore, since the required number of oblivious transfer instances scales with the size of the circuits, oblivious transfer remains as a bottleneck for large-scale multi-party computation implementations. Techniques that allow one to extend a small number of oblivious transfers into a larger one in an efficient way make use of the oblivious transfer variant called randomized oblivious transfer. In this work, we present randomized versions of two known oblivious transfer protocols, one quantum and another post-quantum with ring learning with an error assumption. We then prove their security in the quantum universal composability framework, in a common reference string model.

Why Do Phytoplankton Evolve Large Size in Response to Grazing?

Phytoplankton are among the smallest primary producers on Earth, yet they display a wide range of cell sizes. Typically, small phytoplankton species are stronger nutrient competitors than large phytoplankton species, but they are also more easily grazed. In contrast, evolution of large phytoplankton is often explained as a physical defense against grazing. Conceptually, this explanation is problematic, however, because zooplankton can coevolve larger size to counter this size-dependent escape from grazing. Here, we hypothesize that there is another advantage for the evolution of large phytoplankton size not so readily overcome: larger phytoplankton often provide lower nutritional quality for zooplankton. We investigate this hypothesis by analyzing an eco-evolutionary model that combines the ecological stoichiometry of phytoplankton-zooplankton interactions with coevolution of phytoplankton and zooplankton size. In our model, evolution of cell size modifies the nutrient uptake kinetics of phytoplankton according to known allometric relationships, which in turn affect the nutritional quality of phytoplankton. With this size-based mechanism, the model predicts that low grazing pressure or nonselective grazing by zooplankton favors evolution of small phytoplankton cells of high nutritional quality. In contrast, selective grazing for nutritious food favors evolution of large phytoplankton of low nutritional quality, which are preyed on by medium- to large-sized zooplankton. This size-dependent change in food quality may explain the commonly observed shift from dominance by small picophytoplankton in oligotrophic waters with low grazing pressure to large phytoplankton species in nutrient-rich waters with high grazing pressure.

Epigenetics of Sepsis.

OBJECTIVES: Recent evidence from the fields of microbiology and immunology, as well as a small number of human sepsis studies, suggest that epigenetic regulation may play a central role in the pathogenesis of sepsis. The term "epigenetics" refers to regulatory mechanisms that control gene expression but are not related to changes in DNA sequence. These include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs. Epigenetic modifications, occurring in response to external stressors, lead to changes in gene expression, and thus lie at the intersection between genetics and the environment. In this review, we examine data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsis and that epigenetic therapies may have potential in the treatment of sepsis and its associated organ failures. DATA SOURCES: Online search of published scientific literature via Pubmed using the term "epigenetics" in combination with the terms "sepsis", "infection", "bacterial infection", "viral infection", "critical illness", "acute respiratory distress syndrome", and "acute lung injury". STUDY SELECTION: Articles were chosen for inclusion based on their relevance to sepsis, acute inflammation, sepsis-related immune suppression, and sepsis-related organ failure. Reference lists were reviewed to identify additional relevant articles. DATA EXTRACTION: Relevant data was extracted and synthesized for narrative review. DATA SYNTHESIS: Epigenetic regulation is a key determinant of gene expression in sepsis. At the onset of infection, host-pathogen interactions often result in epigenetic alterations to host cells that favor pathogen survival. In parallel, the host inflammatory response is characterized by epigenetic modifications in key regulatory genes, including tumor necrosis factor and interleukin-1ß. In human sepsis patients, multiple epigenetic modifying enzymes show differential expression in early sepsis, suggesting a role for epigenetics in coordinating the response to infection. In the later stages of sepsis, epigenetic modifications accompany endotoxin tolerance and the immune-suppressed state. In animal models, treatment with epigenetic modifiers can mitigate the effects of sepsis and improve survival as well as reverse sepsis-associated organ injury. CONCLUSIONS: Epigenetic modifications are associated with key phases of sepsis, from the host-pathogen interaction, to acute inflammation, to immune suppression. Epigenetic markers show promise in the diagnosis and prognosis of sepsis and epigenetic modifying agents show promise as therapeutic tools in animal models of sepsis. Human studies in the area of epigenetics are sorely lacking and should be a priority for sepsis researchers.

Epigenetic Profiling in Severe Sepsis: A Pilot Study of DNA Methylation Profiles in Critical Illness.

OBJECTIVES: Epigenetic alterations are an important regulator of gene expression in health and disease; however, epigenetic data in sepsis are lacking. To demonstrate proof of concept and estimate effect size, we performed the first epigenome-wide methylation analysis of whole blood DNA samples from a cohort of septic and nonseptic critically ill patients. DESIGN: A nested case-control study using genomic DNA isolated from whole blood from septic (n = 66) and nonseptic (n = 68) critically ill patients on "Day 1" of ICU admission. Methylation patterns were identified using Illumina 450K arrays with percent methylation expressed as ß values. After quality control, 134 participants and 414,818 autosomal cytosine-phosphate-guanine sites were used for epigenome-wide methylation analyses. SETTING: Tertiary care hospitals. SUBJECTS: Critically ill septic and nonseptic patients. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: A total of 668 differentially methylated regions corresponding to 443 genes were identified. Known sepsis-associated genes included complement component 3; angiopoietin 2; myeloperoxidase; lactoperoxidase; major histocompatibility complex, class I, A; major histocompatibility complex, class II, isotype DR ß I; major histocompatibility complex, class I, C; and major histocompatibility complex, class II, isotype DQ ß I. When compared with whole blood gene expression data from seven external datasets containing septic and nonseptic patients, 81% of the differentially methylated region-associated genes were differentially expressed in one or more datasets and 31% in three or more datasets. Functional analysis showed enrichment for antigen processing and presentation, methyltransferase activity, cell adhesion, and cell junctions. Analysis by weighted gene coexpression network analysis revealed DNA comethylation modules that were associated with clinical traits including severity of illness, need for vasopressors, and length of stay. CONCLUSIONS: DNA methylation marks may provide important causal and potentially biomarker information in critically ill patients with sepsis.

Injury frequency and characteristics (location, type, cause and severity) differed significantly among athletics ('track and field') disciplines during 14 international championships (2007-2018): implications for medical service planning.

OBJECTIVE: To analyse differences between athletic disciplines in the frequency and characteristics of injuries during international athletics championships. METHODS: Study design, injury definition and data collection procedures were similar during the 14 international championships (2007-2018). National medical teams and local organising committee physicians reported all newly incurred injuries daily on a standardised injury report form. Results were presented as number of injuries and number of injuries per 1000 registered athletes, separately for male and female athletes, and for each discipline. RESULTS: From a total of 8925 male and 7614 female registered athletes, 928 injuries were reported in male and 597 in female athletes. The discipline accounting for the highest proportion of injuries was sprints, for both men (24%) and women (26%). The number of injuries per 1000 registered athletes varied between disciplines for men and women: highest in combined events for male athletes (235 (95% CI 189 to 281)) and female athletes (212 (95% CI 166 to 257)), and lowest for male throwers (47 (95% CI 35 to 59)) and female throwers (32 (95% CI 21 to 43)) and for female race walkers (42 (95% CI 19 to 66)). Injury characteristics varied significantly between disciplines for location, type, cause and severity in male and female athletes. Thigh muscle injuries were the main diagnoses in the disciplines sprints, hurdles, jumps, combined events and race walking, lower leg muscle injuries in marathon running, lower leg skin injury in middle and long distance running, and trunk muscle and lower leg muscle injuries in throws. CONCLUSIONS: Injury characteristics differed substantially between disciplines during international athletics championships. Strategies for medical service provision (eg, staff, facilities) during athletics championships should be discipline specific and be prepared for targeting the main injuries in each discipline.

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.

Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers.

BACKGROUND: Breast cancer is a highly heterogeneous disease resulting in diverse clinical behaviours and therapeutic responses. DNA methylation is a major epigenetic alteration that is commonly perturbed in cancers. The aim of this study is to characterize the relationship between DNA methylation and aberrant gene expression in breast cancer. METHODS: We analysed DNA methylation and gene expression profiles from breast cancer tissue and matched normal tissue in The Cancer Genome Atlas (TCGA). Genome-wide differential methylation analysis and methylation-gene expression correlation was performed. Gene expression changes were subsequently validated in the METABRIC dataset. The Oncoscore tool was used to identify genes that had previously been associated with cancer in the literature. A subset of genes that had not previously been studied in cancer was chosen for further analysis. RESULTS: We identified 368 CpGs that were differentially methylated between tumor and normal breast tissue (Ƨ > 0.4). Hypermethylated CpGs were overrepresented in tumor tissue and were found predominantly (56%) in upstream promoter regions. Conversely, hypomethylated CpG sites were found primarily in the gene body (66%). Expression analysis revealed that 209 of the differentially-methylated CpGs were located in 169 genes that were differently expressed between normal and breast tumor tissue. Methylation-expression correlations were predominantly negative (70%) for promoter CpG sites and positive (74%) for gene body CpG sites. Among these differentially-methylated and differentially-expressed genes, we identified 7 that had not previously been studied in any form of cancer. Three of these, TDRD10, PRAC2 and TMEM132C, contained CpG sites that showed diagnostic and prognostic value in breast cancer, particularly in estrogen-receptor (ER)-positive samples. A pan-cancer analysis confirmed differential expression of these genes together with diagnostic and prognostic value of their respective CpG sites in multiple cancer types. CONCLUSION: We have identified 368 DNA methylation changes that characterize breast cancer tumor tissue, of which 209 are associated with genes that are differentially-expressed in the same samples. Novel DNA methylation markers were identified, of which cg12374721 (PRAC2), cg18081940 (TDRD10) and cg04475027 (TMEM132C) show promise as diagnostic and prognostic markers in breast cancer as well as other cancer types.

Is a combined programme of manual therapy and exercise more effective than usual care in patients with non-specific chronic neck pain? A randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effectiveness of a combined intervention of manual therapy and exercise (MET) versus usual care (UC), on disability, pain intensity and global perceived recovery, in patients with non-specific chronic neck pain (CNP). DESIGN: Randomized controlled trial. SETTING: Outpatient care units. SUBJECTS: Sixty-four non-specific CNP patients were randomly allocated to MET (n = 32) or UC (n = 32) groups. INTERVENTIONS: Participants in the MET group received 12 sessions of mobilization and exercise, whereas the UC group received 15 sessions of usual care in physiotherapy. MAIN MEASURES: The primary outcome was disability (Neck Disability Index). The secondary outcomes were pain intensity (Numeric Pain Rating Scale) and global perceived recovery (Patient Global Impression Change). Patients were assessed at baseline, three weeks, six weeks (end of treatment) and at a three-month follow-up. RESULTS: Fifty-eight participants completed the study. No significant between-group difference was observed on disability and pain intensity at baseline. A significant between-group difference was observed on disability at three-week, six-week and three-month follow-up (median (P25-P75): 6 (3.25-9.81) vs. 15.5 (11.28-20.75); P < 0.001), favouring the MET group. Regarding pain intensity, a significant between-group difference was observed at six-week and three-month follow-up (median (P25-P75): 2 (1-2.51) vs. 5 (3.33-6); P < 0.001), with superiority of effect in MET group. Concerning the global perceived recovery, a significant between-group difference was observed only at the three-month follow-up (P = 0.001), favouring the MET group. CONCLUSION: This study's findings suggest that a combination of manual therapy and exercise is more effective than usual care on disability, pain intensity and global perceived recovery.

Illnesses during 11 international athletics championships between 2009 and 2017: incidence, characteristics and sex-specific and discipline-specific differences.

BACKGROUND: Illnesses impair athletes' participation and performance. The epidemiology of illness in athletics is limited. OBJECTIVE: To describe the occurrence and characteristics of illnesses during international athletics championships (indoor and outdoor), and to analyse differences with regards to athletes' sex and participation in explosive and endurance disciplines. METHODS: During 11 international championships held between 2009 and 2017, physicians from both national medical teams and the local organising committees reported daily on all athlete illnesses using a standardised report form. Illness frequencies, incidence proportions (IPs) and rates (IRs), and relative risks (RR) with 95% CIs were calculated. RESULTS: During the 59 days of the 11 athletics championships, 546 illnesses were recorded in the 12 594 registered athletes equivalent to IP of 43.4 illnesses per 1000 registered athletes (95% CI 39.8 to 46.9) or IR of 1.2 per 1000 registered athlete days (95% CI 1.1 to 1.2). The most frequently reported illnesses were upper respiratory tract infections (18.7%), exercise-induced fatigue/hypotension/collapse (15.4%) and gastroenteritis (13.2%). No myocardial infarction was recorded. A total of 28.8% of illnesses were expected to lead to time loss from sport. The illness IP was similar in male and female athletes, with few differences in illness characteristics. During outdoor championships, the illness IP was higher in endurance than explosive disciplines (RR=1.87; 95% CI 1.58 to 2.23), with a considerably higher IP of exercise-induced illness in endurance disciplines, but a similar upper respiratory tract infection IP in both discipline groups. CONCLUSIONS: Illness prevention strategies during international athletics championships should be focused on the most frequent diagnoses in each discipline group.

Eco-Evolutionary Dynamics of Ecological Stoichiometry in Plankton Communities.

Nitrogen (N) and phosphorus (P) limit primary production in many aquatic ecosystems, with major implications for ecological interactions in plankton communities. Yet it remains unclear how evolution may affect the N∶P stoichiometry of phytoplankton-zooplankton interactions. Here, we address this issue by analyzing an eco-evolutionary model of phytoplankton-zooplankton interactions with explicit nitrogen and phosphorus dynamics. In our model, investment of phytoplankton in nitrogen versus phosphorus uptake is an evolving trait, and zooplankton display selectivity for phytoplankton with N∶P ratios matching their nutritional requirements. We use this model to explore implications of the contrasting N∶P requirements of copepods versus cladocerans. The model predicts that selective zooplankton strongly affect the N∶P ratio of phytoplankton, resulting in deviations from their optimum N∶P ratio. Specifically, selective grazing by nitrogen-demanding copepods favors dominance of phytoplankton with low N∶P ratios, whereas phosphorus-demanding cladocerans favor dominance of phytoplankton with high N∶P ratios. Interestingly, selective grazing by nutritionally balanced zooplankton leads to the occurrence of alternative stable states, where phytoplankton may evolve either low, optimum, or high N∶P ratios, depending on the initial conditions. These results offer a new perspective on commonly observed differences in N∶P stoichiometry between plankton of freshwater and those of marine ecosystems and indicate that selective grazing by zooplankton can have a major impact on the stoichiometric composition of phytoplankton.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor.

PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer.

BACKGROUND: Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. MAIN BODY: The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. CONCLUSION: Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.